Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy

Table 1 List of adenosine triphosphate induced cell death core genes and their relationship with tumors

Gene	Full name	Risk factor	Protective factor	Clinical prognostic value	Role in ATP induced cell death	Ref.
P2RX7	Purinergic receptor P2X7	NA	NA	HNSC, KIRC, LAML, SARC	Activates inflammatory mediators and increases calcium ions	Tamajusuku et al[89]
CASP3	Caspase-3	DPG, HNSC, MESO	OV, THYM	ACC, COAD, LGG, LIHC, LUSC, PAAD	Caspase-3 cleavage by caspase-1/4/5/11 forms pores, releasing pro-inflammatory cytokines	Souza et al[90]
PANX1	Pannexin-1	NSCLC, BRCA, RCA, SARC, MESO		LUAD, MESO, PAAD, STAD	P2X7 activation opens PANX1 channels, releasing ATP and triggering cell death pathways	Shoji et al[91]
NLRP3	NOD-like receptor family pyrin domain-containing protein 3	SARC, TGCT	PAAD	LAML, SKCM	NLRP3 activated by stimuli forms inflammasome, triggers caspase-1 activation, releases cytokines, induces apoptosis	Sadatomi et et al[92]
CASP1	Caspase-1	DPG, HNSC, PAAD, LAML, THYM	BRCA, MESO	BRCA, LAML, LGG, MESO, SARC, THYM	Caspase-1 induces cytokine processing, pyrosis, and inflammation	Sadatomi et al[92]
P2RY1	P2Y purinoceptor 1	DPG, PAAD	NA	BLCA, KIRC	P2RY1 can increase calcium ions in the Golgi apparatus	Ohishi et al[93]
P2RY11	P2Y purinoceptor 11	NA	HNSC,PAAD,UCEC, Rb, TGCT	ACC, BLCA, LGG, UCEC, UVM	Involved in immune inflammatory mechanisms	Yoon et al[94]
ORAI1	Calcium release-activated calcium channel protein 1	RCA, SARC, MESO	HNSC	ACC, BLCA, KIRP, LGG, MESO,	Increased intracellular calcium ions	Peng et al[95]
STIM1	Stromal interaction molecule 1	HNSC, PCPG	SARC	KIRP, PAAD, UVM	STIM1 responds to ATP-induced calcium influx, activating ORAI1 and promoting cell death	Peng et al[95]
CASP8	Caspase-8	CESC, RCA	DPG, BRCA, OV, SKCM, SARC	LGG, PAAD, SKCM	CASP8 causes apoptosis	Zeng et al[96]
CASP9	Caspase-9	DPG, NSCLC, ACC, THYM	PAAD,BRCA, Rb, MESO	ACC, BLCA, BRCA, LAML, LGG, MESO	CASP9 causes apoptosis	Zeng et al[96]
CASP7	Caspase-7	HCC, THYM	BRCA, MESO	ACC, KIRC, LGG, LIHC, STAD	CASP7 causes apoptosis	Zeng et al[96]
P2RX3	Purinergic receptor P2X3	DPG	PAAD,NSCLC, CESC, Rb	KIRC, KIRP, LUAD	NA	Ohishi et al[93]
NLRP1	NLR family pyrin domain-containing protein 1	RCA, MESO, THYM	HNSC, NSCLC, SARC	LGG, LUAD, SKCM	NLRP1 activates caspase-1, induces pyrodeath, and releases IL-1β and IL-18	Zhao et al[97]
P2RX4	P2X purinoceptor 4	HNSC, HCC, RCA, Rb, MESO	DPG, UCEC	LGG, LIHC, MESO, UCEC, UVM	P2RX4 contributes to AICD (pyroptosis) by activating the NLRP3 inflammasome, leading to IL-1β and IL-18 production	Ohishi et al[93]
P2RX5	P2X purinoceptor 5	RCA, ACC	HNSC	ACC, KIRC, LGG, SKCM	NA	Ohishi et al[93]
SAPK	Stress-Activated Protein Kinase	NA	NA	NA	ATP induces cell death via SAPK pathways, regulating apoptosis, necrosis, and stress signaling	Humphreys et al[98]
p38 MAPK	p38 mitogen-activated protein kinases (p38 MAPK)	NA	NA	NA	ATP activates p38 MAPK, which leads to cell death through apoptosis and necrosis	Noguchi et al[99]
ASK1	Apoptosis Signal-Regulating Kinase 1	OV, THYM	DPG, HNSC, RCA	KIRC, LAML, LGG, MESO, PAAD, READ, SKCM	Excessive ATP induces cellular stress, activating ASK1 and downstream pathways for cell death	Noguchi et al[99]
NOX2	NADPH oxidase 2	NA	NA	CESC, KIRC, LIHC, LUAD, SKCM	ATP activates NOX2, generating ROS causing oxidative stress and potential cell death	Noguchi et al[99]
bax	BCL2 Associated X	NA	PAAD, BRCA, CESC, RCA	LGG, LIHC, MESO, SKCM, UVM	Excessive ATP triggers BAX activation, mitochondrial dysfunction, and apoptotic cell deat	Wen et al[100]
MLC	Myosin Light Chain	UCEC, MESO	HNSC, PAAD, BRCA, CESC, RCA, PCPG	CESC, KIRC	ATP depletion hampers muscle contraction, affecting myosin function and cellular viability	Hwang et al[101]
ROCK I	Rho-associated, coiled-coil containing protein kinase 1	THYM	BRCA, RCA	KIRC, LGG, PAAD	ATP activates P2X7 receptors, inducing apoptosis via the Rho/ROCK pathway, potentially involving ROCK I	Hwang et al[101]
ERK1/2	Extracellular Signal-Regulated Kinase 1 and 2	NA	NA	NA	ERK1/2 promotes cell survival or antagonizes apoptosis, but prolonged activation may lead to cell death. Activates the ERK1/2 pathway, affecting cell fate	Tsukimoto et al[102]
P2X6	P2X purinoceptor 6	DPG, HNSC, BRCA, OV, UCEC, RCA, MESO	SARC, ACC	ACC, HNSC, KIRC, LGG, OV, UVM	Activation may raise calcium levels, potentially triggering cell death	Banfi et al[103]
CYTC	Cytochrome c	HNSC, NSCLC, Rb, MESO, THYM	DPG, RCA	ACC, BRCA, COAD, HNSC, KIRP, LAML, LGG, LUAD, MESO, UCEC	Cytochrome c released by mitochondria during cell stress triggers cell apoptosis	Sadatomi et al[92]
TNF-α	Tumor necrosis factor alpha	CESC, Rb, MESO	HNSC, PAAD, RCA, SARC	SKCM, THYM	ATP induces cell death, activating TNF-α and triggering apoptosis or necroptosis pathways. Immune cells produce TNF-α in response to ATP, amplifying the cellular response	Hide et al[5]
P2RY5	P2R purinoceptor 5	NA	NA	NA	NA	Yoon et al[94]
P2RY14	P2R purinoceptor14	RCA	HNSC, HCC, OV, UCEC MESO	HNSC, KIRP, LUAD, SKCM, UCEC	NA	Ohishi et al[93]
P2RY13	P2R purinoceptor 13	NA	PAAD, NSCLC, CESC, SKCM, RCA, SARC	ACC, CESC, KIRC, LUAD, SARC, SKCM, UCEC	P2Y13 may play a role in ADP receptors, mainly involved in ATP homeostasis	Ohishi et al[93]
P2RY12	P2R purinoceptor 12	DPG,PAAD,OV, SARC, MESO, THYM,	NSCLC	LAML, LUAD, SKCM	P2Y12 may play a role in ADP receptors, mainly involved in ATP homeostasis	Ohishi et al[93]
P2RY6	P2R purinoceptor 6	DPG, HNSC, PAAD, HCC, BRCA, RCA	SARC,	KIRC, LGG, SKCM, UVM	P2Y6 may be involved in calcium signaling leading to cell death	Ohishi et al[93]
P2RY4	P2R purinoceptor 4	HCC, SARC	HNSC, PAAD, RCA	PRAD	P2Y6 may be involved in calcium signaling leading to cell death	Ohishi et al[93]
P2RY2	P2R purinoceptor 2	DPG, UCEC, BRCA, OV	RCA, SARC	BLCA, GBM, LAML, LGG, MESO, OV, PAAD, UCEC, UVM	ATP binding triggers intracellular signaling pathways that may lead to cell death	Ohishi et al[93]
ANO6	Anoctamin-6	HNSC, PAAD, OV, NSCLC, BRCA, CESC		BRCA, CESC, KIRC, LGG, MESO, OV, PAAD	As a calcium-activating channel and superburning enzyme, it may influence cell death pathways	Ousingsawat et al[104]
cyclinE2	cyclinE2	DPG, HCC, UCEC, RCA, SARC, Rb, ACC, MESO	HNSC	ACC, BRCA, KICH, KIRP, LGG, LIHC, LUAD, MESO, THYM	NA	Wang et al[105]
cyclinD2	Cyclin D2	HNSC	PAAD, NSCLC, BRCA, LAML, MESO, PCPG	LAML, LGG, LUSC, MESO, PAAD, SKCM, THCA, UCEC	NA	Wang et al[105]

ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; COADREAD: Colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; GBMLGG: Glioma; HNSC: Head and neck squamous cell carcinoma; KICH: Kidney chromophobe; KIPAN: Pan-kidney cohort (KICH + KIRC + KIRP); KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Brain lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcomav; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; STES: Stomach and esophageal carcinoma; GCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma.